title: Synthesis of Janus compounds for the recognition of G-U mismatched nucleobase pairs.
abstract: The design and synthesis of two Janus-type heterocycles with the capacity to simultaneously recognize guanine and uracyl in G-U mismatched pairs through complementary hydrogen bond pairing is described. Both compounds were conveniently functionalized with a carboxylic function and efficiently attached to a tripeptide sequence by using solid-phase methodologies. Ligands based on the derivatization of such Janus compounds with a small aminoglycoside, neamine, and its guanidinylated analogue have been synthesized, and their interaction with Tau RNA has been investigated by using several biophysical techniques, including UV-monitored melting curves, fluorescence titration experiments, and (1)H NMR. The overall results indicated that Janus-neamine/guanidinoneamine showed some preference for the +3 mutated RNA sequence associated with the development of some tauopathies, although preliminary NMR studies have not confirmed binding to G-U pairs. Moreover, a good correlation has been found between the RNA binding affinity of such Janus-containing ligands and their ability to stabilize this secondary structure upon complexation.
authors.affiliation: Departament de Química Orgànica, Facultat de Química, Universitat de Barcelona Martí i Franquès 1-11, E-08028 Barcelona, Spain.
authors.forename: Gerard
authors.initials: G
authors.lastname: Artigas
authors.forename: Vicente
authors.initials: V
authors.lastname: Marchán
mesh_terms: D020137:Base Pair Mismatch; D020029:Base Pairing; D002942:Circular Dichroism; D006147:Guanine / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*; D013816:Thermodynamics; D014498:Uracil / Q000737:chemistry*
chemical_list: D008024:Ligands; D014498:Uracil; D006147:Guanine; D012313:RNA